Soonkyu Chung1, Helen Cuffe1, Stephanie M Marshall1, Allison L McDaniel1, Jung-Heun Ha1, Kylie Kavanagh1, Cynthia Hong1, Peter Tontonoz1, Ryan E Temel1, John S Parks2. 1. From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.). 2. From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.). jparks@wakehealth.edu ryan.temel@uky.edu.
Abstract
OBJECTIVE: Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates. APPROACH AND RESULTS: Age-matched, male African Green monkeys (n=5 per group) were assigned to 1 of 3 diets containing 0.002 (low [Lo]), 0.2 (medium [Med]), or 0.4 (high [Hi]) mg cholesterol/kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a stepwise manner in visceral, but not in subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r(2)=0.298; n=15; P=0.035). In visceral fat, dietary cholesterol intake was associated with (1) increased proinflammatory gene expression and macrophage recruitment, (2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and (3) increased expression of proteins involved in FC efflux. CONCLUSIONS: Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates. Visceral fat cells seem to compensate for increased dietary cholesterol by limiting cholesterol uptake/synthesis and increasing FC efflux pathways.
OBJECTIVE: Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates. APPROACH AND RESULTS: Age-matched, male African Green monkeys (n=5 per group) were assigned to 1 of 3 diets containing 0.002 (low [Lo]), 0.2 (medium [Med]), or 0.4 (high [Hi]) mg cholesterol/kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a stepwise manner in visceral, but not in subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r(2)=0.298; n=15; P=0.035). In visceral fat, dietary cholesterol intake was associated with (1) increased proinflammatory gene expression and macrophage recruitment, (2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and (3) increased expression of proteins involved in FC efflux. CONCLUSIONS: Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates. Visceral fat cells seem to compensate for increased dietary cholesterol by limiting cholesterol uptake/synthesis and increasing FC efflux pathways.
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